Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease of adulthood, determined by the loss of spinal, bulbar and cortical motor neurons, which leads to paralysis of voluntary muscles involving also respiratory muscles. ALS was first found in 1869 by French neurologist Jean-Martin Charcot, but it gained international attention in 1939 when the baseball player Lou Gehrig was affected.
Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. Motor neurons are the cells responsible for the contraction of voluntary muscles, involved primarily for movement, but also for vital functions, such as swallowing, phonation and respiration: their degeneration implies the progressive paralysis of the muscles innervated.
The two types of motor neurones that are involved in the disease are upper motor neurones, connecting the brain to the spinal cord, and lower motor neurones, connecting upper motor neurones in the spine to the muscles of the body. These neurones communicate by sending electrical messages from one neurone to another, until they reach the desired location (muscles). In ALS, this line of neuronal communication collapses; motor neurones are unable to bring electrical information from the brain and spinal cord to the muscle, which then becomes inactive (paralysed) as a result. If a muscle is paralysed for a long time, it starts to decrease in mass – it atrophies. This is why muscle wasting is a common symptom of ALS.
A-myo-trophic comes from the Greek language. “A” means no. “Myo” refers to muscle, and “Trophic” means nourishment – “No muscle nourishment.” When a muscle has no nourishment, it “atrophies” or wastes away. “Lateral” identifies the areas in a person’s spinal cord where portions of the nerve cells that signal and control the muscles are located. As this area degenerates, it leads to scarring or hardening (“sclerosis”) in the region.
There are two different types of ALS, sporadic and familial. Sporadic, which is the most common form of the disease, accounts for 90 percent of all cases. It may affect anyone, anywhere. Familial ALS (FALS) accounts for 10 percent of all cases. Familial ALS means the disease is inherited.
We know today the four major genes involved (SOD1, TARDPB, FUS, C9orf72) and about 15 minor genes (i.e. ALS2, SETX, VAPB, FIG4, ERBB4, MATR3, ANG, OPTN, VCP, UBQLN2, CHMP2B, PFN1, hNRPA1 A2 / B1, TUBA4A, NEK1). The mutations identified to date are responsible for about 70% of familial cases and about 12% of sporadic cases. There is vast heterogeneity in the genetic causes of familial ALS, but familial and sporadic ALS have similarities in their pathological and clinical features, suggesting a convergence of the cellular and molecular events that lead to motor neuron degeneration.
In ALS patients cognitive and sensory abilities remain intact in most cases. Up to half of the people living with ALS may also experience difficulties with learning, language and concentration. This is generally known as cognitive impairment. Around 15% of people with ALS experience severe cognitive and behavioural changes that will be diagnosed as frontotemporal dementia (FTD). FTD is an increasingly recognised form of dementia, with different signs and symptoms to the more common Alzheimer’s disease (behavioural changes and speech problems are more prominent in FTD). Mutations in the gene C9ORF72 have been shown to be the most common cause of inherited FTD, ALS and ALS-FTD. Importantly, up to 10% of cases of sporadic ALS (where there is no known family history) are also strongly associated with this same gene.
ALS usually strikes people between the ages of 40 and 70, and it is estimated there are more about 6,000 people with ALS in Italy (although this number fluctuates). However, cases of the disease do occur in persons in their twenties and thirties. The prevalence, i.e. the proportion of population found to be affected by ALS, thanks to the increase of patient taking charge, is increasing. The incidence, i.e.a measure of the probability of occurrence of ALS in the population within a specified period of time, is 1-3 cases per 100,000 inhabitants per year (source: www.aisla.it). Generally though, ALS occurs in greater percentages as men and women grow older. ALS is 20% more common in men than in women. However with increasing age, the incidence of ALS is more equal between men and women.
Life expectancy after diagnosis is between 3-5 years, although its course has different manifestations in each patient that is affected. Twenty percent live five years or more; up to ten percent will live more than ten years. There is some evidence that people with ALS are living longer, at least partially due to clinical management interventions, riluzole and possibly other compounds and drugs under investigation.